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Article

Selective Recognition of Alkyl Pyranosides in Protic and Aprotic Solvents

Supporting Info

Prakash B. Palde^†, Peter C. Gareiss^† and Benjamin L. Miller ^†^‡

Department of Biochemistry and Biophysics and Department of Dermatology, University of Rochester, Rochester, New York 14642

J. Am. Chem. Soc., 2008, 130 (29), pp 9566–9573

DOI: 10.1021/ja802229f

Publication Date (Web): June 25, 2008

†

Department of Biochemistry and Biophysics.

‡

Department of Dermatology.

Abstract

The design and synthesis of receptors capable of selective, noncovalent recognition of carbohydrates continues to be a signature challenge in bioorganic chemistry. We report a new generation of tripodal receptors incorporating three pyridine (compound 2) or quinoline (compound 3) rings around a central cyclohexane core for use in molecular recognition of monosaccharides in apolar and polar protic solvents. These tripodal receptors were investigated using ¹H NMR, UV, and fluorescence titrations in order to determine their binding abilities toward a set of octyl glycosides. Receptor 2 displayed the highest binding affinity reported to date for noncovalent 1:1 binding of an α-glucopyranoside in chloroform (K_a = 212000 ± 27000 M⁻¹) and an approximately 8-fold selectivity for the α anomer over the β anomer of the glucopyranoside. Most importantly, 2 retained its micromolar range of affinities toward monosaccharides in a polar and highly competitive solvent (methanol). The quinoline variant 3 also displayed micromolar binding affinities for selected monosaccharides in methanol (as measured by fluorescence) that were generally smaller than those of 2. Compound 3 was found to follow a selectivity pattern similar to that of 2, displaying higher affinities for glucopyranosides than for other monosaccharides. The binding stoichiometry was estimated to be 1:1 for the complexes formed by both 2 and 3 with glucopyranosides, as determined by Job plots. Nuclear Overhauser effect spectroscopy allowed for the derivation of a binding model consistent with the observed selectivities.